This article reviews the current legislative requirements for risk assessment of combined exposure to multiple chemicals via multiple exposure routes, focusing on human health and particularly on food-related chemicals. The aim is to identify regulatory needs and current approaches for this type of risk assessment as well as challenges of the implementation of appropriate and harmonized guidance at international level. It provides an overview of the current legal requirements in the European Union (EU), the United States and Canada...

The incidence rates of a wide range of diseases and conditions have increased over the last decades. There is controversy over the origin of these increases, whether they are caused by exposure to compounds thought to have an effect on the endocrine system, the "endocrine disruption theory", or whether some other factor is responsible. In this analysis, the authors take a closer look at the role that changes in reproductive factors have played in this respect. They apply the relative risks of age at first pregnancy and parity or family size to a set of Dutch demographic data from 1955 and 2015 and calculate the percentage of disease increase explained...

There has been a steady output of epidemiological studies linking environmental and occupational exposures to altered telomere length, showing mainly positive associations with persistent organic pollutants, inverse association with cadmium and inconsistent results with arsenic and lead. A bell-shaped dose-response relationship has been observed for ionizing radiation with telomere shortening at a low dose. Long-term air pollution is associated with telomere shortening, whereas the short-term exposure studies have shown mixed results...

Drugs, cosmetics, preservatives, fragrances, pesticides, metals, and other chemicals can cause skin sensitization. The ability to predict the skin sensitization potential and potency of substances is therefore of enormous importance to a host of different industries, to customers' and workers' safety. Animal experiments have been the preferred testing method for most risk assessment and regulatory purposes but considerable efforts to replace them with non-animal models and in silico models are ongoing. This review provides a comprehensive overview of the computational approaches and models that have been developed for skin sensitization prediction over the last 10 years...

Chlorofluorocarbons (CFCs) were introduced in the 1930s as the safe replacements for the toxic and flammable refrigerants being used at that time. Subsequently, hydrochlorofluorocarbons (HCFCs) were also developed. In addition to refrigerant applications, they were used as foam blowing agents, as solvents and as propellants for many aerosols. In the 1970s and 1980s, concern developed about their environmental impact, specifically on stratospheric ozone depletion. Industry began to consider acceptable replacements...

Perhaps no other topic in risk analysis is more difficult, more controversial, or more important to risk management policy analysts and decision-makers than how to draw valid, correctly qualified causal conclusions from observational data. Statistical methods can readily quantify associations between observed variables using measures such as relative risk (RR) ratios, odds ratios (OR), slope coefficients for exposure or treatment variables in regression models, and quantities derived from these measures. Textbooks of epidemiology explain how to calculate population attributable fractions, attributable risks, burden-of-disease estimates, and probabilities of causation from relative risk (RR) ratios...

Scientific databases were searched for terms applicable to karyomegaly in renal tubules of laboratory animals used in preclinical safety evaluation studies, and in humans. Renal tubule karyomegaly was more frequently reported in the rat in response to chemical exposure compared to other laboratory animal species. Renal tubule karyomegaly also occurred in the mouse in response to chemical insult, but much less commonly than in the rat. This nuclear lesion was recorded infrequently for hamster, dog, guinea pig, rabbit, pig, and non-human primate...

This review provides an overview of results obtained when using proteome analysis for detecting sex-based differences in response to toxicants. It reveals implications to be taken into account when considering the use of proteomics in toxicological studies. It appears that results may differ when studying the same chemical in the same species in different target tissues. Another result of interest is the limited dose-response behavior of differential abundance patterns observed in studies where more than one dose level is tested...

The objective was to perform a thorough review of published and other available data to elucidate the extent of chemical skin injuries in the US. Chemical skin injuries differ significantly from skin lesions produced by other injury mechanisms, so this review was restricted to the former. Retrieval of relevant published data was performed in PubMed and Google. Other data were retrieved from the American College of Surgeons National Trauma Databank, American Burn Association National Burn Repository, US Department of Labor Bureau of Labor Statistics, websites of all 50 US States Departments of Health, and the National Poison Data System of the American Association of Poison Control Centers...

The aryl hydrocarbon receptor (AHR) is not essential to survival, but does act as a key regulator of many normal physiological events. The role of this receptor in toxicological processes has been studied extensively, primarily employing the high-affinity ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, regulation of physiological responses by endogenous AHR ligands remains to be elucidated. Here, we review developments in this field, with a focus on 6-formylindolo[3,2-b]carbazole (FICZ), the endogenous ligand with the highest affinity to the receptor reported to date...

This article summarizes recent experimental and epidemiological data on the genotoxic and carcinogenic activities of cobalt compounds. Emphasis is on the respiratory system, but endogenous exposure from Co-containing alloys used in endoprostheses, and limited data on nanomaterials and oral exposures are also considered. Two groups of cobalt compounds are differentiated on the basis of their mechanisms of toxicity: (1) those essentially involving the solubilization of Co(II) ions, and (2) metallic materials for which both surface corrosion and release of Co(II) ions act in concert...

Decision on the safety margin, for instance by using uncertainty factors (UFs), is a key aspect in setting Occupational Exposure Limits (OELs). We analyzed the UFs in 128 OEL recommendations from the European Commission's Scientific Committee on Occupational Exposure Limits (SCOEL). We investigated factors expected to potentially influence the UFs, as well as a selection of factors that might influence how expert groups perceive quality or reliability of key studies. We extracted UFs explicitly stated in the recommendations (EUFs) and, when EUFs were missing, calculated an implicit safety margin (ISM) by dividing the point of departure (PoD) by the OEL...